Lysophosphatidic Acid (LPA)-antibody (504B3) Engagement Detected by Interferometry Identifies Off-target Binding

Overview

Journal Lipids Health Dis

Publisher Biomed Central

Specialties Biochemistry
Endocrinology

Date 2021 Apr 15

PMID 33853612

Authors

Manisha Ray

Yasuyuki Kihara

Darryl J Bornhop

Jerold Chun

Affiliations

Soon will be listed here.

Abstract

Background: Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that acts through its six cognate G protein-coupled receptors. As a family, lysophospholipids have already produced medicines (e.g., sphingosine 1-phosphate) as is being pursued for LPA through the use of specific antibodies that reduce ligand availability.

Methods: The binding properties of a commercially available, reportedly specific, monoclonal LPA antibody named 504B3 that is related to the clinical candidate Lpathomab/LT3015 were reexamined using a free solution assay (FSA) measured in a compensated interferometric reader (CIR).

Results: Measurement of 504B3 binding properties with an FSA-CIR approach revealed similar binding affinities for 504B3 against LPA as well as the non-LPA lipids, phosphatidic acid (PA) and lysophosphatidylcholine (LPC).

Conclusions: Antibody binding specificity and sensitivity, particularly involving lipid ligands, can be assessed in solution and without labels using FSA-CIR. These findings could affect interpretations of both current and past basic and clinical studies employing 504B3 and related anti-LPA antibodies.

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